Substantia nigra hyperechogenicity with LRRK2 G2019S mutations

Background:: Transcranial sonography (TCS) area of hyperechogenicity in the substantia nigra (aSN) is increased in idiopathic and genetic Parkinson's disease (PD). Methods:: We performed TCS in 34 LRRK2 G2019S mutation carriers manifesting PD, 24 non-manifesting mutation carriers, and 28 idiopathic PD patients and compared them with 40 healthy controls (total, n = 126). Results:: Compared with the controls (mean 0.15 cm²), the aSN values in all other groups were increased. The mean aSN was 0.23 cm² in nonmanifesting mutation carriers (P =.015), 0.34 cm² in idiopathic PD patients (P <.0001), 0.32 cm² in LRRK2-associated PD patients (P <.0001), and 0.33 cm² in the overall PD group (P <.0001). LRRK2-associated PD patients had a higher aSN than did nonmanifesting carriers (P =.011), but there was no significant difference in aSN between patients with idiopathic and LRRK2-associated PD (P =.439). Conclusions:: Our results suggest that SN pathoanatomical alterations may not be substantially different between idiopathic and LRRK2-associated PD. The findings in the nonmanifesting mutation carriers suggest the presence of intermediate nigrostriatal pathology consistent with the age-dependent reduced penetrance of this mutation.